Date of Award

2024

Document Type

Open Access Master's Report

Degree Name

Master of Science in Biomedical Engineering (MS)

Administrative Home Department

Department of Biomedical Engineering

Advisor 1

Muhammad Rizwan

Committee Member 1

Sangyoon Han

Committee Member 2

Shiyue Fang

Abstract

Biomaterials that integrate multiple functionalities, mimic the extracellular matrix (ECM) microenvironment to support cellular growth, and adhere robustly to damaged tissues are highly needed to advance tissue engineering. Protein-based biomaterials are promising due to their inherent biocompatibility, biomimicry, biodegradation, and cell-supportive properties. Herein, by leveraging the unique ability of dithiolanes to generate on-demand in-situ thiols, we developed a new class of dithiolane-modified, protein-based biomaterial that combines unique, seemingly opposing functions for tissue engineering. Dithiolane-modified gelatin, a model protein used herein, enabled photoinitiator-free photo-crosslinking to form multi-functional gelatin-dithiolane (GelDT) hydrogels, which displayed exceptional long-term stability in cell culture media (>28 days) to support the growth of both surface-seeded and encapsulated cells. GelDT hydrogels allowed pre-gelation tuning of biomechanical properties and biodegradation via introducing physical crosslinks, and post-gelation tuning of matrix stress-relaxation rate, via responding to exogenous thiols, independently of other parameters. Furthermore, GelDT enabled glutathione-responsive drug release, and demonstrated robust tissue adhesion (in-vivo) due to covalent disulfide coupling with endogenous tissue thiols. Together, this study presents a novel multi-responsive and multi-functional protein-based biomaterial, anticipated to advance the field of tissue engineering and regeneration.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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